Genetic and molecular basis of nervous system disorders – Rochellys Diaz Heijtz group

Our research interests are centered on understanding the biological basis of neurodevelopmental disorders, with a focus on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

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Research focus

We use different animal model systems to understand the contribution of genetic factors, impact of early adverse life experience (e.g., stress, infections), and gene-environment interactions on the development of motor, affective and cognitive functions, which are impaired in ADHD and ASD. In parallel, we conduct human studies using several cohorts of infants and children (e.g., infants with elevated likelihood of developing ASD, children with ASD and a population-based Swedish twin cohort).

Our work is performed in collaboration with clinicians and psychologists at the Astrid Lindgren Children's Hospital and Karolinska Institutet Center of Neurodevelopmental Disorders (KIND). This optimizes the opportunities for iterative translation from basic to clinical research and back to more fundamental mechanistic studies.

Key subjects of interest:

  • Potential role of gut microbiota on early aspects of motor, social and cognitive development in humans
  • Influence of gut-derived microbial molecules such as “bacterial peptidoglycan fragments” on typical and atypical brain development
  • Role of bacterial peptidoglycans and their sensing molecules in brain and behavior across the life span.
  • Potential beneficial effects of psychobiotic diet in early life on motor, social and cognitive development
Illustration of Biological signaling pathways and molecules involved in the microbiota-gut-brain axis
Biological signaling pathways and molecules involved in the microbiota-gut-brain axis. Photo: Rochellys Diaz Heijtz

There are multiple direct and indirect pathways through which gut microbiota may influence the brain, including signals carried by neuronal circuits [e.g., bidirectional vagus nerve-to-brain communication, the enteric nervous system and neuropods; (1)], the production of bacterial fermentation metabolic by-products, such as short chain fatty acids (2), tryptophan metabolites and neurotransmitters (3), release of cytokines by immune cells (4), and gut hormone signaling (5). The gut microbiota has been shown to influence various neurodevelopmental processes such as microglial maturation and function, blood brain barrier formation and integrity, myelination and neurogenesis (7). For more details, see Gonzalez-Santana A, Diaz Heijtz R, Trends Mol Med 2020 08;26(8):729-743.

Recent Scientific Discoveries

Autism Spectrum Disorder (ASD) is now understood to be a multifactorial neurodevelopmental condition, involving genetic susceptibility, environmental risk factors, and gene-environmental interactions. One such risk factor is having a sibling with ASD, with studies consistently demonstrating a  higher prevalence among siblings and in families with a history of ASD.

In a recent prospective longitudinal study published in Translational Psychiatry, we found pronounced alterations in the gut microbiota composition of infants at elevated likelihood (EL) of developing ASD (i.e., siblings of children with ASD) compared to low-likelihood (LL) infants (i.e., infants without a family history of ASD) at five months of age  (see Figure 1). Specifically, infants in the EL group harbored less beneficial Bifidobacterium species (B. bifidum, B. longum and B. Bifidobacterium kashiwanohense) and more Clostridium (C. bolteae, C. difficile, C. clostridioforme, C. neonatale) species compared to infants in the LL group. On the other hand, Clostridium species have been previously been with linked to ASD, are considered pathobionts and responsible for inflammation when homeostasis is disturbed.

Chart showing Gut microbiota composition level of infants at EL and LL of ASD from 5 to 36 months of age. Reprinted with permission from Zuffa et al., 2023)
Figure 1: Gut microbiota composition level of infants at EL and LL of ASD from 5 to 36 months of age. The relative mean abundance of the top taxa was calculated using the aggregated OTUs at the genus level. The largest differences between the two groups were observed at 5 months of age. The LL group harbored more Bifidobacteria (51% vs. 26%), while the EL group had more Akkermansia (3% vs. 0.003%), Enterobacter (5% vs. 0.006%), Clostridium (5% vs. 0.005%) and Klebsiella (6% vs. 0.004%) species compared to the LL group. (Reprinted with permission from Zuffa et al., 2023).

Publications

Selected publications

Fetal, neonatal, and infant microbiome: Perturbations and subsequent effects on brain development and behavior.
Diaz Heijtz R
Semin Fetal Neonatal Med 2016 12;21(6):410-417

Host microbiota modulates development of social preference in mice.
Arentsen T, Raith H, Qian Y, Forssberg H, Diaz Heijtz R
Microb Ecol Health Dis 2015 ;26():29719

Normal gut microbiota modulates brain development and behavior.
Diaz Heijtz R, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S
Proc Natl Acad Sci U S A 2011 Feb;108(7):3047-52

Staff and contact

Group leader

All members of the group

Contact and visit us

Contact information for the Diaz Heijtz laboratory at the Department of Neuroscience, Karolinska Institutet.

Postal address

Karolinska Institutet
Department of Neuroscience
171 77 Stockholm

Visiting address (visitors, couriers, etc.)

Karolinska Institutet
Biomedicum, D8
Solnavägen 9
171 65 Solna

Delivery address (goods, parcels, etc.)

Tomtebodavägen 16
171 65 Solna

Map: Karolinska Institutet, Biomedicum, Solnavägen 9

Scientific activities

Symposia

  • Keynote speaker at the 4th International World of Microbiome Conference 2023, Grand Hotel Millennium Sofia, Bulgaria, 26-28 October 2023
  • Co-organiser of the 11th IBRO World Congress of Neuroscience, Granada, Spain 9-13 September 2023:  "Microbiota-Gut-Brain Axis as a Modulator of Brain Function and Dysfunction"

Appointments

  • Honorary Professor, Old Herborn University, Germany on 15 June 2023

Doctoral thesis

Part of the Adjudication Committee of the doctoral thesis Gezime Seferi, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Norway. Title of thesis: "Hippocampal lipid droplets and the gut microbiome: Effects of type 2 diabetes and exercise"

 

Picture gallery

Rochellys Diaz Heijtz to the right, among other Honoray Professors.
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